There is an increasing interest in small natural biomolecules using them in different aspects in biomedicine, nanotechnology and material science. Virus simulators, virus capsids or virus-like particles are very attractive because of their regular structure, their homogenous particle size, their stability, the ease of production and the potential for manipulation. Virus-like particle possess dynamic structures, their interior is accessible and furthermore the coat is modifiable. Dependent on the application the virus-like particles could have an envelope or not and could be chosen as virus simulators. These embodiments could be used as new biological entities or targets, as vaccines, as antigens for antibody production, as research tools, as diagnostic tool, for drug delivery and bioconjunctions. These virus simulators are formed by self-assembly of envelope and or capsid proteins of many viruses. The size varies between 22-150 nm dependent on the morphology of the particular virus. The virus simulators are non-infectious because they assemble without incorporating genetic material. Dependent on the application foreign genetic material could be included in the herein described virus simulator.
A promising application of these virus simulators is the production of vaccines against various diseases because their repetitive, high density display of epitopes elicit often a strong immune response. The small size of particles is an advantage for uptake by dendritic cells. Chimeric virus simulators offer an enormous potential in selective, multi-epitope, multi-protein, multi-serotype, multi-strain, or multi-species presentation.
There exist many expression systems for the production of virus simulators which include the baculovirus/insect cell system, various mammalian cell lines, either stably or transiently transfected or transduced with viral expression vectors, furthermore various species of yeast including Saccharomyces cerevisiae and Pichia pastoris, and Escherichia coli and other bacteria.
Vaccination is dependent on the generation of a sufficient immunity to protect from infectious diseases. The mostly used attenuated virus vaccines rely on limited replication of the virus in the host following immunization. But this kind of vaccination may cause severe reactions in some patients. Therefore the development of virus-like particles (VLP) as subunit vaccines is an advantage because the particles lack in general DNA or RNA genome but have the authentic conformation of the natural virus.
Vaccination is one of the most potent and cost-effective counter-measures to the threat of e.g. seasonal or pandemic influenza outbreaks. The ease of spread as an aerosol and the cause for a severe illness especially to susceptible humans are the major reasons why influenza is one of the most devastating viral diseases. Currently licensed seasonal vaccines are only partially protective, and the egg-based production is very time-consuming and cost-intensive. This strategy is vulnerable to the unanticipated emergence of epidemic strains that are poorly matched or not matched at all by the vaccine. Due to the danger of emerging strains of avian influenza or influenza of other origin novel vaccine approaches are necessary.
In another aspect the research in the field of several important viruses like HCV, HIV, Ebola etc. is very difficult because of biosafety issues. Until now there exist only a few models for investigation of viral entry and viral trafficking. Diagnostic tools are based on the genome of these viruses because of the lack of appropriate non-infectious virus models.
Presently commercial human influenza vaccines contain hemagglutinin as their only or main viral antigen. Their production starts from viruses grown on embryonated chicken eggs or, more recently, in mammalian cells in tissue culture. The production in eggs requires selection of high yield, reassorted virus strains, is limited in capacity, time-consuming (6-8 months), and expensive. Beyond that it can cause problems in vaccinated persons allergic to egg protein. The production is only possible with non-lethal bird strains. One of the most important disadvantages of the egg-based production is the limited capacity. In case of a pandemic the production of the seasonal influenza vaccine has to be stopped in favour of a pandemic influenza vaccine production which could result in even more lethal events in the long run.
Vaccines against viral diseases rely traditionally on attenuated virus strains or inactivation of infectious virus. An appropriate environment is necessary for highly pathogenic or haemorraghic viruses which constrains the production possibilities because of the biosafety level (e.g. BL3/BL4). For some viruses like human papilloma virus the attenuation will not be sufficient because the virus cannot be propagated in vitro. The ability to generate human papilloma virus (HPV)-like particles based vaccines (Gardasil, Cervarix) has changed the prospects for preventing cervical cancer in woman.
Due to the danger of emerging strains of avian influenza or other origin, novel vaccine approaches are necessary which result in an enhanced protection.